Related Experiment Video
Updated: Jun 9, 2026
05:27
Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools
Published on: July 20, 2022
Mitochondria limit coenzyme Q export under cholesterol biosynthetic stress
Marjana Ndoci1, Sharanya Bhattacharya1, Ishita Agrawal2
1Metabolism and Cell Death Institute, Molecular Targets and Therapeutics Centre, Helmholtz Zentrum München , Neuherberg, Germany.
The Journal of Cell Biology
|June 8, 2026
Summary
The mevalonate pathway regulates Coenzyme Q (CoQ) distribution. Mitochondria prioritize CoQ retention during metabolic stress, preserving respiration but increasing ferroptosis risk.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Regulation
Background:
- Coenzyme Q (CoQ) is a vital hydrophobic lipid synthesized mainly in mitochondria.
- Intracellular CoQ distribution pathways remain largely uncharacterized.
- The mevalonate pathway produces isopentenyl pyrophosphate (IPP), a precursor for both CoQ and cholesterol.
Purpose of the Study:
- To investigate the role of the mevalonate pathway in regulating intracellular Coenzyme Q distribution.
- To understand how metabolic pathway flux affects CoQ levels and cellular CoQ distribution.
Main Methods:
- Analysis of Coenzyme Q synthesis and distribution under varying mevalonate pathway activity.
- Investigating the impact of HMG-CoA reductase (HMGCR) upregulation and downregulation on CoQ and cholesterol levels.
- Assessing mitochondrial CoQ retention and extramitochondrial CoQ availability.
Main Results:
- Coenzyme Q synthesis remains stable despite mevalonate pathway flux changes.
- HMGCR upregulation enhances cholesterol ester synthesis without altering CoQ levels.
- Pathway downregulation preserves mitochondrial CoQ by reducing export, maintaining respiration but increasing ferroptosis sensitivity.
Conclusions:
- The mevalonate pathway critically regulates Coenzyme Q distribution.
- Mitochondria actively manage CoQ retention to sustain respiratory function during metabolic stress.
- Prioritizing mitochondrial CoQ leads to reduced extramitochondrial CoQ and heightened ferroptosis susceptibility.
Related Concept Videos
01:30The Electron Transport Chain
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
01:45Mitochondrial Membranes
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
01:45Mitochondrial Membranes
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:29Cholesterol: Significance and Regulation
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
01:43Electron Transport Chain: Complex III and IV
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...